Trisomy 21 (prenatal diagnosis)

Definition

• Chromosomal aberration with an extra copy of chromosome 21; it is the most common viable autosomal trisomy and the leading genetic cause of intellectual disability.

Classification

• About 95% result from meiotic non-disjunction, usually of maternal origin, and about 4% from translocations (most commonly t(14;21)); mosaicism due to non-disjunction during embryonic development is less common.

Occurrence & epidemiology

Epidemiology

• In the United States the incidence is about 1 in 700 live births; the risk rises with maternal age from about 1 in 1,476 at 20 through 1 in 352 at 35 to 1 in 85 at 40.
• Because most births occur to younger women, only about 20% of children with Down syndrome are born to mothers over 35.

Clinical features

Prenatal signs and clinical features

• Typical features are intellectual disability, muscular hypotonia, characteristic craniofacial features and various malformations.
• About 50% of neonates have congenital heart disease, most often ventricular septal defect and atrioventricular septal defect; about 6% have gastrointestinal anomalies, particularly duodenal atresia.

Diagnosis

Biochemical markers

• A typical pattern for trisomy 21 is low PAPP-A and high free beta-hCG.
• In trisomy 18 or 13, however, both values are low, which is a clear difference from the pattern in trisomy 21.
• The risk calculation is improved by additional markers such as the nasal bone, ductus venosus and tricuspid regurgitation.

• First-trimester combined screening measures maternal serum beta-hCG and PAPP-A together with nuchal translucency; in trisomy 21, beta-hCG is typically raised, PAPP-A low and nuchal translucency enlarged, although no nuchal translucency threshold is diagnostic.
• Cell-free DNA analysis in maternal plasma is possible from 10 weeks and has higher detection rates than older methods but remains a screening test; the diagnosis is confirmed by karyotyping, prenatally for example after chorionic villus sampling.

Keep learning in the app

Further reading (selection)

1. StatPearls: Down Syndrome (NCBI Bookshelf)
2. MSD Manual Professional Edition: Down Syndrome (Trisomy 21)
3. MSD Manual Professional Edition: Noninvasive Prenatal Fetal Screening Tests
4. DocCheck Flexikon, Ersttrimesterscreening

Cross-references